Janet T. Jones

Increased oviposition and growth in immature Biomphalaria glabrata after exposure to Schistosoma mansoni.

Biomphalaria glabrata snails are known to be castrated by infection with the trematode parasite Schistosoma mansoni 4-6 weeks post-infection. The pattern of oviposition in the first 35 days post-exposure (p.e.) was investigated, in snails aged 14 weeks and measuring 7-10 mm diameter which had not commenced egg-laying, by counting the numbers of eggs laid in 7-day intervals. A group of exposed snails was compared with a control non-exposed group. The exposed group included both parasitized and non-parasitized snails, and showed a significant increase in the median number of eggs laid during the periods 14-21 and 22-28 days p.e. Throughout the entire 35-day period exposed non-parasitized snails laid significantly more eggs than control snails, while parasitized snails laid significantly more eggs than controls during days 22-28 p.e. and significantly fewer during days 29-35 p.e. Parasitized snails also laid significantly more eggs/egg mass in the period 16-28 days p.e. than did control snails. Growth of the snails was measured. By day 28 p.e. the mean diameter of the exposed group was significantly greater than that of the control group. The increase in oviposition by snails soon after exposure is discussed in terms of a compensatory response for expected future suppression of egg-laying. The fact that parasitized and non-parasitized snails both show increased oviposition indicates that normal development of the parasite is not necessary to trigger the response.

Schistosome fecundity: influence of host genotype and intensity of infection.

The host genetic influence on the fecundity of Schistosoma mansoni was studied by measuring egg excretion and accumulation of eggs in the tissues of two inbred strains of mice. The two strains, NIH/Ola and CBA/Ca, differed in both parameters. Egg excretion after infection in the NIH/Ola reached a maximum and declined earlier than was the case for the CBA/Ca mice. More eggs accumulated in the gut and lungs of CBA/Ca, while the NIH/Ola had more eggs in the liver by 100 days post-infection. Statistical analysis of both tissue eggs and faecal eggs, using a robust, non-parametric method, indicated that there is significant evidence for a density dependent reduction in fecundity of worms in more heavily infected animals. We conclude that both the genetic constitution of the murine host and the intensity of infection affect the fecundity of Schistosoma mansoni worms.

Praziquantel efficacy against schistosomiasis mansoni in schoolchildren in north-west Ethiopia

The efficacy of praziquantel against schistosomiasis mansoni has been measured in 10-14 years old schoolchildren in a highly endemic area of north-west Ethiopia. The egg reduction rate was 97% and the cure rate was 94%, as assessed by a single Kato smear. No evidence for praziquantel resistance was detected.

The influence of the h-2 complex on responses to infection by schistosoma mansoni in mice.

In order to determine whether a given H-2 haplotype has similar effects on responses to schistosomiasis mansoni on different genetic backgrounds, mice of 2 pairs of congenic strains (H-2b and H-2k on BALB/c and C57BL/10 backgrounds) were infected. Worm burdens, mortality, splenomegaly, tissue and faecal egg counts, and antibody titres to worm and egg antigens were measured. The genetic background had a major effect on the genesis of splenomegaly, on the deposition of eggs in the spleen, the maximum faecal egg count, the antibody titre to egg and worm antigens and the rate of generation of antibody response. The H-2 haplotype was shown to consistently influence the maximum faecal egg count and the antibody titres. Worm burden was not influenced by genetic differences between strains and mortality differences were not significant. The data presented here indicate that the effect of the major histocompatibility complex on responses to infection is greatly influenced by the genetic background on which it is expressed.

Variation in susceptibility of Schistosoma mansoni to damage by polycations

We have studied the characteristics of binding of the polycation poly-L-lysine to the schistosome surface. Two consequences of this binding were measured: (a) tegumental damage, as assessed by the uptake of the DNA binding stain Hoechst 33258, and (b) the effect of cation binding on the uptake of a lipid analogue, 5-(N-octadecanoyl) aminofluorescein. Schistosomes were incubated with a preparation of eosinophil cationic proteins; these naturally occurring polycations bound to and damaged the parasites in a manner similar to poly-L-lysine. The different developmental stages of the parasite vary in the degree to which the poly-L-lysine binds, in susceptibility to tegumental damage, and in the degree to which lipid uptake is affected. The lung stage is most resistant to damage, and 3-week-old worms are the most susceptible. The teguments of male and female adult worms differ in the binding of the poly-L-lysine. Individual schistosomula, and batches of schistosomula shed at different times, show non-genetic variation in binding and susceptibility to damage. These findings may relate to variation in immune killing in vivo.

Inhibition of protein synthesis in irradiated larvae of Schistosoma mansoni

Summary UV‐irradiated and gamma‐irradiated schistosomula of Schistosoma mansoni induce high levels of resistance to challenge infection in experimental hosts. It was observed that both types of irradiation severely inhibited protein synthesis by the parasite larvae. Schistosomula were treated with the metabolic inhibitor actinomycin D to simulate this effect of irradiation. The ability of these drug‐treated larvae to induce immunity was tested in animal protection experiments. Our results suggest that inhibition of protein synthesis may help to generate the enhanced immunogenicity of irradiated schistosomula. In explanation, we propose that irradiated schistosomula may be such potent immunogens because they express antigens in disrupted, abnormal conformations. Inhibition of protein synthesis may both directly create such modified antigens, and also ensure that they persist and accumulate for presentation to the host immune system.

The inheritance of responses to schistosomiasis mansoni in two pairs of inbred strains of mice.

Genetic differences in mice influence both the pathological and immunological responses to schistosomiasis mansoni. We have investigated the nature of the genetic factors influencing these responses by crossing two different pairs of strains of mice which vary in their response to infection, and measuring responses in the F1 hybrid and backcross offspring. The two pairs of parental strains differed with respect to faecal egg excretion, accumulation of eggs in the tissues, splenomegaly and pattern of antibody response. The numbers of adult worms which establish do not differ between strains. The inheritance of the responses measured was different in the two pairs of strains. The F1 hybrid from the C57BL/6/0la X BALB/c cross resembled the low-responding parental strain (C57BL/6/0la) with respect to faecal egg excretion, accumulation of eggs in the tissues and splenomegaly, and was intermediate in its pattern of antibody response. The F1 hybrid mice from the NIH X CBA/Ca cross resembled the high-responding strain (CBA/Ca) with respect to faecal egg excretion, accumulation of eggs in the tissues and splenomegaly, and had an earlier and greater antibody response than either parental strain. No evidence of single gene influence on any of these responses was seen in the backcross offspring. The differing patterns of inheritance and the absence of a bimodal distribution of responses in the backcross offspring indicate that each of these responses is influenced by multiple genes. The pattern of antibody response did not correlate between strains with any of the pathological responses. The positive correlation of egg accumulation in the tissues and faecal egg excretion suggests that there are genetic influences on the fecundity of the worms.

An in vivo model for the study of chemotaxis induced by schistosomula of Schistosoma mansoni.

Peritoneal leucocytosis, with an increased percentage of eosinophils, was found in mice which had been infected with Schistosoma mansoni for 7 weeks or longer. Specific IgG against worm and egg antigens increased in peritoneal fluids and their corresponding sera respectively 5 and 7 weeks after infection. An intraperitoneal challenge with schistosomula elicited neutrophilia in all mice regardless of immune status, as well as infiltration of eosinophils and macrophages in infected mice. The secondary eosinophilia occurred in mice previously infected for 1 week or longer, whereas the infiltration of macrophages occurred only after worms from the primary infection had started laying eggs. Unlike the eosinophilia the macrophage response required infection with bisexual populations of cercariae. Injection of previously infected mice with Escherichia, Trichinella or Toxocara failed to increase the proportions of eosinophils and macrophages. Schistosomula-induced eosinophilia could be elicited in passively sensitized mice. Intraperitoneal injection of PBS extract of adult worms elicited eosinophilia in infected mice and neutrophilia in normal mice. Two chromatographic fractions induced eosinophilia and the third only neutrophilia. The relevance of these observations to host response to S. mansoni infections is discussed.